Pharmaceutical compositions of bortezomib

Abstract

The present invention relates to a sterile, ready-to-use, aqueous composition of bortezomib that is stable over its shelf life.

1 . A sterile, ready-to-use, aqueous composition comprising 1 to 2.5 mg/ml of bortezomib, sufficient tonicity adjusting agent to provide an osmolality of from about 280 mosm/kg to about 360 mosm/kg, a solvent, a cosolvent and a pH of from about 4.5 to about 6.5, wherein the tonicity adjusting agent is mannitol, the solvent is ethanol, the cosolvent is propylene glycol, and wherein upon storage at 25° C. and 60% relative humidity for six months, the bortezomib content in the composition is not less than 90%, and the amount of impurities is as follows—
 a. Impurity B not more than 0.5% w/v, 
 b. Impurity C not more than 0.5% w/v, 
 c. Impurity I not more than 0.5% w/v, 
 d. Impurity J not more than 0.5% w/v, and 
 e. Total impurities not more than 3.5% w/v. 
 
     
     
         2 . The sterile, ready-to-use, aqueous composition of  claim 1  wherein the composition is free of preservatives. 
     
     
         3 . (canceled) 
     
     
         4 . The sterile, ready-to-use, aqueous composition of  claim 3  wherein the amount of mannitol used ranges from about 1% w/v to about 5% w/v. 
     
     
         5 . The sterile, ready-to-use, aqueous composition of  claim 1  wherein the solvent and cosolvent are together present in an amount ranging from about 0.05% w/v to about 5% w/v. 
     
     
         6 . (canceled) 
     
     
         7 . The sterile, ready-to-use, aqueous composition of  claim 1 , wherein the composition further comprises a stabilizer and wherein the stabilizer is present in an amount ranging from about 0.01% w/v to about 2% w/v. 
     
     
         8 . The sterile, ready-to-use, aqueous composition of  claim 7  wherein the stabilizer is selected from the group consisting of arginine, alanine, glycine, methionine, lysine or proline, or a derivative or salt thereof, and mixtures thereof. 
     
     
         9 . The sterile, ready-to-use, aqueous composition of  claim 1  further comprising a chelating agent. 
     
     
         10 . The sterile, ready-to-use, aqueous composition of  claim 9  wherein the chelating agent is selected from DOTA (1, 4, 7, 10 tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid), EDTA (Ethylenediaminetetraacetic acid), ODDA (1, 4, 10, 13-tetraoxa-7, 16-diazacyclooctadecane-7), EGTA (ethylene glycol-bis (β-aminoethyl ether)-tetraacetic acid). 
     
     
         11 . The sterile, ready-to-use, aqueous composition of  claim 10  wherein the chelating agent is present in an amount of at least 0.005% w/v.